Microscope Hats Peer Inside Mice Brains

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Mice are the mainstay of modern biomedical research, but the
ability to image their brain cells while they're scampering
around is no easy task. Scientists at Stanford University have
created a powerful mini-microscope that can fit on a mouse head
and stay there without interfering with the mouse's actions.

"It's like a little high tech hat," said Mark Schnitzer, an
associate professor of biological sciences and applied physics at
Stanford who led the development with Stanford engineering
professor Abbas El Gamal. "The mouse can behave very naturally
and freely."

Although the individual parts aren't novel by themselves, they do
create a tiny little novel system when combined. The microscope
is an advancement of an earlier one that Schnitzer's lab designed
in 2008. Unlike that one, the latest fluorescence microscope
integrates all the optical parts into 1.9 grams so that there are
no ancillary components to make it bulky. The technology is
described in the latest issue of the journal Nature
Methods.

Before the 2008 microscope, optical studies on mice brains
usually required the animals to be held in place or walk on a
moving platform keeping their heads still. Although that method
had some advantages, it required training the mice. By affixing
tiny microscopes to mice heads, scientists hope to learn more
about function in the poorly understood cerebellum, the part of
the brain that controls motor coordination and balance.

The new mini-microscope looks like a boxy Lincoln-style top hat.
Inside are special filters, little lenses, a camera made from
semiconductor sensors, a mirror, an objective, and a tiny LED for
illumination.

The tiny scope has strong capabilities. Image sensors made from a
metal-oxide semiconductor have the capability of doing
intelligent pixel-by-pixel image analysis. A test of the new tech
showed that their microscope can count cells and even detect
tuberculosis bacterial labeled with a fluorescent stain.

The scientists point out that although the microscope is more
powerful than their previous version, the parts could be
mass-produced rather inexpensively, making the tiny hats more
affordable.

For example, the optoelectronic parts cost between $25,000 and
$50,000 for their last microscope, but the mass produced versions
only cost between about $1 and $10 for the new one.

Portability is another advantage, giving researchers the
opportunity to shove a few microscopes in their pocket and bring
sophisticated analysis capabilities with them.

"You could take the technology into areas that conventional
microscopes can't visit," Schnitzer said. "That would allow one
to perform microbiology diagnostics in areas that are poorly
serviced by conventional microscopy."

Next, the scientists plan to use the technology to examine other
parts of the mouse brain. Schnitzer and his co-authors also have
equity in a startup that aims to commercialize the
mini-microscope technology.

David Kleinfeld is a physics professor at the University of
California San Diego who also teaches neuroscience. He said he
thinks the new microscope should reinvigorate research into part
of the brain that humans are embarrassingly ignorant about.

"The system as a whole represents an order of magnitude
improvement in size and price point over past designs," Kleinfeld
said. "[It] may lead to a quantum jump in the ubiquity of imaging
in biomedical research."